Ethyl bromoacetate → ethyl 3-fluoro-5-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenoxyacetate

HRID 890879Notes

Reaction equation

HRID 890879 reaction equation
Br[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[F:8][C:9]1[CH:10]=[C:11]([OH:23])[CH:12]=[C:13]([C:15]2([O:21][CH3:22])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[CH:14]=1.C([O-])([O-])=O.[K+].[K+]>CN(C)C=O>[F:8][C:9]1[CH:10]=[C:11]([CH:12]=[C:13]([C:15]2([O:21][CH3:22])[CH2:16][CH2:17][O:18][CH2:19][CH2:20]2)[CH:14]=1)[O:23][CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4]

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 11430Potassium CarbonateHCID 117362763-Fluoro-5-(4-methoxytetrahydro-2H-pyran-4-yl)phenol

Product 1

HCID 22246123ethyl 3-fluoro-5-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenoxyacetateYield 73.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of ethyl bromoacetate (0.5 g, 3 mmol), 3-fluoro-5-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenol (Example 8, Step 4) (0.3 g, 1.3 mmol) and K2CO3 (0.11 g, 0.8 mmol) in dimethylformamide (5.0 mL) was stirred at room temperature for 16 h under an argon atmosphere. The reaction mixture was partitioned between 5% citric acid (25 mL) and EtOAc (25 mL). The organic phase was washed with water, dried (Na2SO4), filtered and concentrated. The resulting syrup was purified by flash column chromatography on silica gel, eluting with 25% EtOAc in hexane, to give 0.3 g (73%) of ethyl 3-fluoro-5-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenoxyacetate as a colorless viscous liquid: 1H NMR (CDCl3/300 MHz) δ 6.77 (d, 2H, J=10.5 Hz), 6.52 (d, 1H, J=10.5 Hz), 4.61 (s, 2H), 4.28 (q, 2H, J=6.9 Hz), 3.82 (m, 4H), 2.99 (s, 3H), 1.92 (m, 4H), 1.31 (t, 3H, J=6.9 Hz). FABMS m/z=313 (M+H). HRMS calcd for C16H22FO5 313.1451, found 313.1399.

Workup

  1. customThe reaction mixture was partitioned between 5% citric acid (25 mL) and EtOAc (25 mL)
  2. washThe organic phase was washed with water
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting syrup was purified by flash column chromatography on silica gel
  7. washeluting with 25% EtOAc in hexane

Sources & evidence

ORD record
ord-5ba4f945e0e14b1f96b2aeaa68b9783c
Source dataset
uspto-grants-2006_02
Patent number
US06998415B2

Reaction notes

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